Regulation of bone homeostasis by controlling osteoclasts and osteoblasts
| Project/Area Number |
24390359
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Keio University |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2012: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
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| Keywords | 骨代謝 / 破骨細胞 / 骨芽細胞 / 骨粗鬆症 / Blimpl / 分化 / 骨 |
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| Outline of Final Research Achievements |
Bone homeostasis is regulated in a delicate balance between bone resorbing osteoclasts and bone forming osteoblasts. In this study, we found that B lymphocyte induced maturation protein 1 (Blimp1) plays a crucial role in regulating osteoclastogenesis and bone mass at an adult stage, and targeting Blimp1 in adult mice resulted in significant inhibition of osteoclast formation followed by increased bone mass. We also found that osteoclast stimulatory transmembrane protein (OC-STAMP) is required for osteoclast cell-cell fusion, and OC-STAMP-deficient mice exhibited complete abrogation of osteoclast cell-cell fusion. We further found that B cell lymphoma 6 (Bcl6) plays a role in regulating osteoblastogenesis via suppressing expression of signal transducer and activator of transcription 1 (Stat1), and Bcl6-deificient osteoblasts showed altered differentiation owing to Stat1 elevation. Bcl6/Stat1 doubly deficient mice exhibited reversed osteoblastogenesis compared with Bcl6-deficient mice.
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Report
(4 results)
Research Products
(38 results)
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[Journal Article] Interleukin-1 receptor-associated kinase-4 (IRAK4) promotes inflammatory osteolysis by activating osteoclasts and inhibiting formation of foreign body giant cells.2015
Author(s)
Katsuyama E, Miyamoto H, Kobayashi T, Sato Y, Hao W, Kanagawa H, Fujie A, Tando T, Watanabe R, Morita M, Miyamoto K, Niki Y, Morioka H, Matsumoto M, Toyama Y, Miyamoto T.
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Journal Title
J Biol Chem.
Volume: 290
Pages: 716-726
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Mycobacterium tuberculosis promotes arthritis development through toll-like receptor 2.2015
Author(s)
Kanagawa H, Niki Y, Kobayashi T, Sato Y, Katsuyama E, Fujie A, Hao W, Miyamoto K, Tando T, Watanabe R, Morita M, Morioka H, Matsumoto M, Toyama Y, Miyamoto T.
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Journal Title
J Bone Miner Metab.
Volume: 33
Pages: 135-141
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Bcl6 promotes osteoblastogenesis through Stat1 inhibition.2015
Author(s)
Fujie A, Funayama A, Miyauchi Y, Sato Y, Kobayashi T, Kanagawa H, Katsuyama E, Hao W, Tando T, Watanabe R, Morita M, Miyamoto K, Kanaji A, Morioka H, Matsumoto M, Toyama Y and Miyamoto T.
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Journal Title
Biochem Biophys Res Commun.
Volume: 457
Pages: 451-456
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] TNFα promotes osteosarcoma progression by maintaining tumor cells in an undifferentiated state2014
Author(s)
Mori T, Sato Y, Miyamoto K, Kobayashi T, Shimizu T, Kanagawa H, Katsuyama E, Fujie A, Hao W, Tando T, Iwasaki R, Kawana H, Morioka H, Matsumoto M, Saya H, Toyama Y and Miyamoto T
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Journal Title
Oncogene
Volume: 印刷中
Pages: 4236-4241
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] The Vitamin D Analogue ED71 but Not 1,25(OH)2D3 Targets HIF1α Protein in Osteoclasts.2014
Author(s)
Sato Y, Miyauchi Y, Yoshida S, Morita M, Kobayashi T, Kanagawa H, Katsuyama E, Fujie A, Hao W, Tando T, Watanabe R, Miyamoto K, Morioka H, Matsumoto M, Toyama Y, Miyamoto T.
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Journal Title
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] HIF1 α is required for osteoclast activation by estrogen deficiency in postmenopausal osteoporosis2013
Author(s)
Miyauchi Y, Sato Y, Kobayashi T, Yoshida S, Mori T, Kanagawa H, Katsuyama E, Fujie A, Hao W, Miyamoto K, Tando T, Morioka H, Matsumoto M, Chambon P, Johnson RS, Kato S, Toyama Y, Miyamoto T.
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Journal Title
Proc Natl Acad Sci U S A
Volume: 110
Pages: 16568-16573
DOI
Related Report
Peer Reviewed
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[Journal Article] Twist2 functions as a tumor suppressor in murine osteosarcoma cells2013
Author(s)
Ishikawa T, Shimizu T, Ueki A, Yamaguchi S, Onishi N, Sugihara E, Kuninaka S, Miyamoto T, Morioka H, Nakayama R, Kobayashi E, Toyama Y, Mabuchi Y, Matsuzaki Y, Yamaguchi R, Miyano S and Saya H
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Journal Title
Cancer Science
Volume: (in press)
Pages: 880-8
DOI
Related Report
Peer Reviewed
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[Journal Article] Conditional inactivation of Blimp1 in adult mice promotes increased bone mass.2012
Author(s)
Miyauchi Y, Miyamoto H, Yoshida S, Mori T, Kanagawa H, Katsuyama E, Fujie A, Hao W, Hoshi H, Miyamoto K, Sato Y, Kobayashi T, Akiyama H, Morioka H, Matsumoto M, Toyama Y, Miyamoto T
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Journal Title
Journal of Biological Chemistry.
Volume: vol. 287
Pages: 28508-17
DOI
Related Report
Peer Reviewed
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